The structure of fluticasone propionate is illustrated as follows:

6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate (Compound 1) is utilized as an intermediate (or a key or important intermediate) in the synthesis of fluticasone propionate. The structure of Compound 1 is illustrated as follows:

Fluticasone propionate may be synthesized by way of the oxidation of flumethasone to yield Compound 1, which may be reacted to obtain fluticasone propionate. The synthetic route for the foregoing synthesis may be generally illustrated as shown in FIG. 1.
Dimethylthiocarbamoyl chloride may be used as a sulfation agent in the above-identified process. Then, the resultant product may be decomposed by refluxing to obtain diethylamine and the thioic acid, Compound 1. However, pollution is generated by that method due, at least in part, to the relatively high consumption of reagents. Additionally, the yield obtained by using diethylamine is low. Diethylamine may also be used as a decomposing agent, but the generation of pollution and low yield have also been observed when diethylamine is used as the decomposing agent.
To facilitate the discussion of the subject matter disclosed herein, Compound 2 is defined herein as 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid, Compound 3 is defined herein as 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carboxylic acid, and Compound 4 is defined herein as 17β-[(N,N-dimethyl carbamoyl)thio]carbonyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene. Compounds 2-4 are illustrated as follows:

Compound 1 may be generated by reacting Compound 3 with dimethylthiocarbamoyl chloride and sodium iodide in 2-butanaone to obtain Compound 4, which may then be reacted with a hydrolyzing agent, such as sodium hydrosulfide or sodium thiomethoxide, to generate the sodium salt of Compound 1. The sodium salt of Compound 1 may be alkylated in-situ with chlorofluoromethane to yield fluticasone propionate, or the sodium salt of Compound 1 may be acidified to obtain Compound 1, which may also be isolated and converted to fluticasone propionate by alkylation with chlorofluoromethane. When Compound 4 is hydrolyzed by utilizing sodium hydrosulfide or sodium thiomethoxide, however, excess sodium hydrosulfide or sodium thiomethoxide may generate toxic hydrogen sulfide or methyl mercaptan. If the alkylation of the sodium salt of Compound 1 is direct, excess sodium hydrosulfide may react with chlorofluoromethane, and thus, more chlorofluoromethane may be required (e.g., to compensate for the chlorofluoromethane that reacts with the excess sodium hydrosulfide). Further, the resultant impurity of such processes is difficult to remove, thereby affecting (or reducing) the quality (or purity) of the final product.